Pack containing soft capsules

ABSTRACT

The invention relates to a pack comprising a packaging material and soft capsules, to a process for the stabilisation of soft capsules, and to a process for the production of the pack.

The invention relates to a pack comprising a packaging material and soft capsules, to a process for the stabilisation of soft capsules, and to a process for the production of the pack.

Soft capsules are capsules which, owing to additions of softeners, such as, for example, glycerol, sorbitol, maltitol and polyethylene glycols, present in the capsule shell, have a certain elasticity and softness and are employed for the administration of various substances, such as, for example, medicaments, food supplements and/or functional ingredients. Soft capsules can be produced, for example, on the basis of gelatine or starch. Gelatine-based soft capsules have long been known as soft gelatine capsules and are commercially available from various suppliers. Starch-based soft capsules are a relatively new development, an example thereof are soft capsules marketed by Swiss Caps, Switzerland, under the trade name Vega-Gels®.

If liquid or semi-solid substances are to be administered by means of the soft capsules, they can be encapsulated directly, solids are first dissolved or suspended in liquid or semi-solid bases, such as, for example, fats, oils, wax mixtures or polyethylene glycols, possibly in combination with emulsifiers. Depending on the method of administration, such as, for example, orally, rectally or vaginally, soft capsules can have various shapes, they can be, for example, round, oval, oblong or torpedo-shaped. Soft capsules can be produced by the processes known in the prior art, such as, for example, by the Scherer process, the Accogel process or the droplet or blowing process.

The softening action of the softener component present in the shells of soft capsules is essentially based on the hygroscopicity thereof and the associated inclusion of water the capsule shell. At room temperature (22° C./45 to 65% RH (RH=relative humidity)), soft capsules have a water content of about 7 to 8% by weight. If the water content is significantly below this, for example due to excessively dry storage or drying, this results in embrittlement of the capsule shell, with the consequence of increased fragility of the capsule wall and the formation of cracks. If the water content is significantly above this, for example due to excessively moist storage, swelling of the capsule shell and sticking together of the soft capsules occur. Both excessively dry and also excessively moist storage also result in unpredictable effects on the substances to be administered and any further auxiliaries present, meaning that the supply with the substances present therein that is intended with the taking of soft capsules can no longer be ensured. Varying environmental influences result in totally incalculable influences on the stability of soft capsules, meaning that their shelf life, i.e. the period over which the soft capsules are within the respective specifications applying to them which have to be met in order that they can be taken as intended, can no longer be predicted with the requisite certainty. This is unacceptable, in particular also for safety reasons.

The object of the present invention was to find a simple and inexpensive way of avoiding the losses in quality arising both with embrittlement of the capsule shell and also due to swelling and sticking together and significantly increasing the shelf life of soft capsules at high dryness, high atmospheric humidity, possibly also together with high temperatures, as prevail, for example, in climatic zones III and IV, and also in the case of strongly varying atmospheric humidity.

The object has been achieved, surprisingly, by introducing the soft capsules into a packaging material in the inside wall(s) of which an absorbent and at least one channel former is embedded, at least over part of the area. The invention thus relates to a pack comprising a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and at least one soft capsule, where the soft capsule(s) is (are) present in the container.

Surprisingly, the storage of the soft capsules results in an increase in the shelf life, although the container with an absorbent an agent is present which results in a drying action. This is because drying of soft capsules results, via the removal of water, precisely in embrittlement and fragility of the capsule shell or even cracking, i.e. precisely the state that is avoided by the invention.

According to an advantageous embodiment, the pack according to the invention contains soft gelatine capsules as soft capsules. The invention therefore relates to a pack which is characterised in that the soft capsule(s) present therein is (are) (a) soft gelatine capsule(s).

According to a further advantageous embodiment, the pack according to the invention contains as starch-based soft capsules. The invention therefore relates to a pack which is characterised in that the soft capsule(s) present therein is (are) (a) starch-based soft capsule(s).

The container is resealable and can have any spatial shape, such as, for example, that of a cylinder or cuboid, provided that it is sufficiently large to accommodate the soft capsules inside.

Resealable means that the container can be opened and re-closed repeatedly, i.e. at least once, preferably a number of times, particularly preferably at least as often as corresponds to the number of soft capsules present in the container. The container is so tightly sealed after each opening and closing operation that ingress of moisture and gases into the interior of the container is effectively prevented.

Opening and sealing of the container is carried out by a tightly sealing closure matched to the container. All types of closures can be employed so long as they ensure that gases and/or moisture cannot penetrate into the interior of the container in the closed state, or can only do so in extremely small amounts, even after repeated opening and closing of the container.

According to an embodiment of the invention, lids are used as closure. Examples of lids are screw caps, caps which are inverted over the upper edge of the vessels, or introduced into the interior of the vessel. In the case of spatial shapes which have corners, such as, for example, cuboids, the corners of the opening and the matching lid may also be slightly rounded in order to increase the tightness of the container against gases and moisture.

According to a preferred embodiment, the container has a cuboid-shaped spatial shape, rounded corners and is readily stackable. An embodiment of this type is depicted by way of example in FIG. 1. The container comprises walls (2) whose inward-facing sides contain, at least over part of the area, at least one channel former together with at least one absorbent, has rounded corners (7) and has a lid (1) as closure.

The absorbents and channel formers present in the container may jointly either be present directly in the inside wall(s) of the polymer forming the container or be applied as a layer to the inside wall(s) of the polymeric container. Likewise, absorbents and channel formers may be embedded in an inlay, which is introduced into the container as insert, so that at least part of the inside walls of the container are lined thereby.

Inside wall(s) is taken to mean the inward-facing surface of the wall/walls of the container, i.e. the surface(s) of the container which is (are) in contact with the soft capsule(s) present therein.

Suitable materials for the container are polymers. Polymers, which can be employed in a mixture with absorbents and channel formers, are, in particular, thermoplastics, such as, for example, polyolefins, such as polyethylene and/or polypropylenes, polyisoprenes, polybutadienes, polybutenes, polysiloxanes, polyamides, ethylene-vinyl acetate copolymers, ethylene-methacrylate copolymers, polystyrenes, polyesters, polyanhydrides, polyacrylate nitriles, polysulfonates, polyester amides, polyacrylate esters, propylene-maleic anhydride, polyethylene-maleic anhydride, polyethylene-urethanes, polyethylene-ethyl-vinyl alcohols, polyethylene-nylon and/or polyurethanes. The walls provided with absorbents and channel formers on their inside surface have, based on the total weight of the mixture of polymer, channel formers and absorbents, a content of polymer of 10-90% by weight.

Absorbents which may be present are in principle any type of desiccants, i.e. moisture-binding binders. Three groups of desiccants come into consideration:

The first group contains chemical substances which form hydrates with water. Examples of chemical substances of this type are anhydrous salts, which tend to absorb water or moisture, and form a stable hydrate in the process. The moisture is bound, and liberation thereof is prevented by a chemical reaction.

The second group of desiccants contains substances which are reactive. The substances react with water or moisture by forming a new substance. The newly formed substances are normally stable at low temperatures, which is only reversible with expenditure of high energy. Desiccants of this type are used principally for drying solvents and as water-absorbent material in polymers which themselves have to remain in a moisture-reduced state.

The third group of desiccants binds the moisture by physical adsorption. The desiccant contains particles having fine capillaries into which the moisture is drawn. The pore size of the capillaries and the density thereof in the desiccant determine the absorption properties. Examples of desiccants of this type are molecular sieves, silica gels, certain synthetic polymers, such as, for example, those which are used in babies' nappies, and starches. Desiccants from the third group are preferably present in the container since they are substantially inert and water-insoluble. Particular preference is given here to molecular sieves having a pore size of 3 to 15 Ångström and/or silica gels having a pore size of 24 Ångström.

Suitable channel formers are hydrophilic substances, such as, for example, polyglycols, ethylvinyl alcols, glycerol, polyvinyl alcohols, polyvinylpyrrolidone vinylpyrrolidone, N-methylpyrrolidone, polysaccharides, saccharides and/or sugar alcohols. Preferred polyglycols are polyethylene glycol and/or polypropylene glycol. Saccharides which can be used are, for example, glucose, mannose, galactose and/or fructose. Suitable sugar alcohols are, for example, mannitol, sorbitol, hexitol, dulcitol, xylitol, ribitol and/or erythrol. Polysaccharides are taken to mean, for example, dextrins and/or hydrolysed starch.

In the inside walls provided with absorbents and channel formers, the channel formers can have a proportion of 10-40% by weight, based on the total weight of the mixture of polymer, channel formers and absorbents.

Absorbents and channel formers are embedded over part of the surface or over the entire area in the inside walks) of the container. Over part of the area means that at least part of the total area of the container forming the inside wall(s) comprises absorbents and channel formers.

Over the entire area means that the entire area of the container forming the inside walls comprises absorbents and channel formers. According to an advantageous embodiment, absorbents and channel formers are present in at least 10%, preferably in at least 50%, particularly preferably in at least 90%, of the inside walls, based on the total inside surface area of the container.

Containers made from polymers which comprise absorbents and channel formers and which are suitable as container for the pack according to the invention are known in the prior art and are described, for example, in WO 97/32663 A1, EP 1000873 A2 and WO 03/086900 A1, EP 1421991 A1. Containers which can be employed in the pack according to the invention are commercially available and are available, for example, from Capitol Specialty Plastics Inc., 2039 McMillan Street Auburn, Ala., USA, under the trade name Activ-Vial or from Süd Chemie, Ostenrieder Str. 15, 85368 Moosburg, Germany, under the trade name 2 AP Multipolymer.

The pack according to the invention is produced by dispensing the soft capsule(s) into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and subsequently sealing the container. The present invention therefore also relates to a process for the production of a pack, which is characterised in that the soft capsule(s) is (are) introduced into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and the container is subsequently sealed.

The pack according to the invention results in an increase in the shelf life of the soft capsules present therein. The invention therefore also relates to a process for increasing the shelf life of soft capsules, which is characterised in that they are introduced into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and the container is subsequently sealed.

The stabilising action of the pack according to the invention is based on the influence of the container on the in soft capsule(s), which can consequently be made available with a long shelf life. Achievement of the action according to the invention thus requires that the soft capsule(s) is (are) present in the container, i.e. the soft capsule(s) and container are together in the form of a pack.

Besides the stabilising action on the soft capsule shell, in the pack according to the invention also results in stabilisation of the active compounds and/or auxiliaries present therein, i.e. the entire formulation. This applies, in particular, if the active compounds and/or auxiliaries present are sensitive to moisture. Examples of moisture-sensitive active compounds which are thus preferably present in the soft capsules in the pack are many pharmaceutical active compounds, such as hormones or proteins, vitamins, cells, such as, for example, probiotic cultures.

The examples explain the invention without being restricted thereto.

EXAMPLE 1 Investigation of the Stability of Soft Capsules in the Pack According to the Invention Compared with Soft Capsules in Conventional Packaging Materials

Multivitamin soft capsules (active-compound composition and capsule shell as described below) are introduced individually into a thermoformed cavity film made from PVC 250 μm+40 g/m² of PVDC and heat-sealed with aluminium foil (20 μm) and into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent (type: M-3006-16 Activ-Vial) in the inside walls of which a molecular sieve having a capacity of 1.92 g is embedded.

The blisters and containers containing the multivitamin soft capsules are stored at 40° C. and 75% relative humidity (RH), removed from storage after predetermined times, assessed visually with respect to their appearance and investigated analytically with respect to the amounts of active compound present. The results are compiled in Tables 1 and 2.

TABLE 1 Product Multivitamin soft capsule* Batch 9018401 Packaging material PVC/PVDC-aluminium blister Storage condition 40° C./75% RH Storage duration Start 3 months Parameter mg/capsule % mg/capsule % Ascorbic acid 209 100 159 76 Dexpanthenol 13.5 100 9.7 72 Thiamine*HCL 19.7 100 17.1 87 Cyanocobalamine 0.199 100 0.171 86 Folic acid 0.62 100 0.57 92 *Composition of the soft capsule shell: gelatine 209.76 mg, glycerol 85% 65.83 mg, sorbitol solution 70% 44.21 mg, black iron oxide 1.22 mg, red iron oxide 3.89 mg.

TABLE 2 Product Multivitamin soft capsule* Batch 9018802 Packaging material Container in the inside walls of which a channel former and an absorbent are embedded Storage condition 40° C./75% RH Storage duration Start 6 months Parameter mg/capsule % mg/capsule % Ascorbic acid 213 100 210 99 Dexpanthenol 13.3 100 12.8 96 Thiamine*HCL 19.6 100 19.3 98 Cyanocobalamine 0.21 100 0.173 82 Folic acid 0.60 100 0.520 87 *Composition of the soft capsule shell: gelatine 209.76 mg, glycerol 85% 65.83 mg, sorbitol solution 70% 44.21 mg, black iron oxide 1.22 mg, red iron oxide 3.89 mg.

EXAMPLE 2 Investigation of the Stability of Soft Capsules in the Pack According to the Invention

Multivitamin soft capsules (active-compound composition and capsule shell as described below) are introduced into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent (type: M-3006-16 Activ-Vial) in the inside walls of which a molecular sieve having a capacity of 1.92 g is embedded.

The multivitamin soft capsules are stored at 30° C. and 65% relative humidity (RH), removed from storage after predetermined times, assessed visually with respect to their appearance and investigated analytically with respect to the amounts of active compound present. The results are compiled in Table 3.

TABLE 3 Product Multivitamin soft capsule* Batch GD 06 0045 Packaging material Container in the inside walls of which a channel former and an absorbent are embedded Storage condition 30° C./65% RH Storage duration Start 6 months Parameter mg/capsule % mg/capsule % β-Carotene 2.3 100 2.0 87 Thiamine nitrate 2.40 100 2.37 99 Riboflavin 2.09 100 2.23 107 Nicotinamide 20.6 100 20.1 98 Pyridoxine*HCL 3.60 100 3.39 94 Ascorbic acid 120.5 100 115.0 95 Tocopherol acetate 20.0 100 19.8 99 Folic acid 0.581 100 0.603 104 Biotin 0.176 100 0.185 105 Cyanocobalamine 0.0163 100 0.0158 97 Calcium panthotenate 15.6 100 14.9 96 *Composition of the soft capsule shell: gelatine, glycerol 98-100%, sorbitol solution 70%, water 

1. Pack comprising a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and at least one soft capsule, where the soft capsule(s) is (are) present in the container.
 2. Pack according to claim 1, characterised in that the soft capsule(s) is (are) (a) soft gelatine capsule(s).
 3. Pack according to claim 1, characterised in that the soft capsule(s) is (are) (a) starch-based soft capsule(s).
 4. Pack according to claim 1, characterised in that the container has a cuboid-shaped basic shape.
 5. Pack according to claim 1, characterised in that the container contains, as absorbent, a desiccant which binds moisture by physical adsorption.
 6. Pack according to claim 5, characterised in that the desiccant is a molecular sieve or silica gel.
 7. Process for the production of a pack according to claim 1, characterised in that the soft capsule(s) is (are) introduced into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and the container is subsequently sealed.
 8. Process for increasing the shelf life of soft capsules, characterised in that they are introduced into a resealable container in/on the inside wall(s) of which at least one channel former is embedded, at least over part of the area, together with at least one absorbent, and the container is subsequently sealed. 